Quinolone derivatives and salts thereof, preparation processes thereof, and antibacterial agents containing the same

Abstract

Antibacterial quinolone derivatives represented by the following formula and salts thereof are disclosed. ##STR1## wherein R 1 meawns a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted lower alkenyl group or a substituted or unsubstituted phenyl group, R 2 denotes a hydrogen atom or a carboxyl-protecting group, R 3 represents a hydrogen or halogen atom or an amino, mono- or di-(lower alkyl)amino, hydroxyl or lower alkoxyl group, X is a hydrogen or halogen atom, Y means a nitrogen atom or a group C-R 4 in which R 4 is a hydrogen or halogen atom or a lower alkyl or lower alkoxyl group or is a group ##STR2## which forms a ring together with R 1 (i.e., the asterisked carbon atoms are linked to the N(1) atom of the quinolone skeleton), and A denotes a specific N-containing group. Preparation processes of the quinolone derivatives and antibacterial agents containing the same are also disclosed.

We claim: 
     
       1. A compound of the formula I or a pharmaceutically acceptable salt thereof: ##STR114## wherein R 1  is lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, C 3  -C 7  -cycloalkyl, lower alkyl-C 3  -C 7  -cycloalkyl, lower alkenyl, phenyl or substituted phenyl, wherein the substituents are independently selected from the group consisting of halo, lower alkoxy, acetyloxy, hydroxy, amino, lower alkyl and nitro; R 2  denotes a hydrogen atom, lower alkyl, aralkyl, aryl, lower alkanyloxy-lower alkyl, lower alkoxy-carbonyloxy-lower alkyl, lower alkoxymethyl, di(lower alkyl)amino-lower alkyl; (5-methyl-2-oxol-4-yl)methyl, or phthalidyl; R 3  represents hydrogen, halo, amino, mono- or di-(lower alkyl)amino, hydroxy or lower alkoxy; X is hydrogen or halo; Y is C--R 4  in which R 4  is hydrogen, halo, lower alkyl or lower alkoxy, A denotes a substituted or unsubstituted 3-oxazolidinyl group or a substituted or unsubstituted tetrahydro-1,3-oxazin-3-yl group wherein said substituents are independently selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl, mono- or di-(lower alkyl)amino-lower alkyl, hydroxy, lower alkoxy, amino, and mono- or di(lower alkyl)amino; --Z--(CH 2 ) n  --B is which Z is an oxygen atom or a group H--R 5 , wherein R 5  is hydrogen, lower alkyl or benzyl, B is selected from the group consisting of ##STR115##  wherein B' means an oxygen or sulfur atom or N--R 8 , n' groups of R 6  may be the same or different and individually mean a hydrogen atom or a lower alkyl group; R 7  is a member selected from the group consisting of formidoyl, acetimidoyl and benzimidoyl; R 8  and R 9  are the same or different and are selected from the group consisting of hydrogen, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, methoxy-lower alkyl, amino-lower alkyl, lower alkoxycarbonyl; carboxy-lower alkyl; C 3  -C 5  -cycloalkyl, benzyl, acetyl, benzoyl, trifluoroacetyl, lower alkoxycarbonyl and benzyloxycarbonyl and l stands for an integer of 1-3, m is 1, n' an integer of 1-4, o an integer of 0 or 1, p an integer of 0-2, and q an integer of 0 or 1, the sum of o+p+q being 2; and n stands for an integer of 0-2, provided that R 1  is not ethyl when R 6  is hydrogen. 
     
     
       2. An antibacterial composition comprising a carrier and, as an active ingredient, an antibacterially effective amount of the quinolone derivative or a pharmaceutically acceptable salt thereof according to claim 1. 
     
     
       3. A quinoline derivative according to claim 1, 1-cyclopropyl-6,8-difluoro-7-(5-hydroxymethyl-3-oxazolidinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid or a pharmaceutically acceptable salt thereof. 
     
     
       4. An antibacterial composition comprising a carrier and, as an active ingredient, an antibacterially effective amount of the quinoline derivative or a pharmaceutically acceptable salt thereof according to claim 3. 
     
     
       5. A compound of the formula I or a pharmaceutically acceptable salt thereof: ##STR116## wherein R 1  is lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, C 3  -C 7  -cycloalkyl, lower alkyl-C 3  -C 7  -cycloalkyl, lower alkenyl, phenyl or substituted phenyl, wherein the substituents are independently selected from the group consisting of halo, lower alkoxy, acetyloxy, hydroxy, amino, lower alkyl and nitro; R 2  denotes a hydrogen atom, lower alkyl, aralkyl, aryl, lower alkanoyloxy-lower alkyl, lower alkoxy-carbonyloxy-lower alkyl, lower alkoxymethyl, di(lower alkyl)amino-lower alkyl; (5-methyl-2-oxol-4-yl)methyl, or phthalidyl; R 3  represents hydrogen, halo, amino, mono- or di(lower alkyl)amino, hydroxyl or lower alkoxy; X is hydrogen or halo; Y is C--R 4  in which R 4  is hydrogen, halo, lower alkyl or lower alkoxy, A denotes a substituted or unsubstituted 3-oxazolidinyl group or a substituted or unsubstituted tetrahydro-1,3-oxazin-3-yl group wherein said substituents are independently selected from the group consisting of lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, amino-lower alkyl, mono- or di-(lower alkyl)amino-lower alkyl, hydroxyl, lower alkoxy, amino, and mono- or di(lower alkyl)amino; --Z--(CH 2 ) n  --B in which Z is an oxygen atom or a group N--R 5 , wherein R 5  is hydrogen, lower alkyl or benzyl, B is selected from the group consisting of ##STR117##  wherein B' means an oxygen or sulfur atom or N--R 8 , n' groups of R 6  may be the same or different and individually mean a hydrogen atom or a lower alkyl group; R 7  is a member selected from the group consisting of halo-lower alkyl, hydroxy-lower alkyl, methoxy-lower alkyl, amino-lower alkyl, cyano-lower alkyl, ethoxycarbonyl-lower alkyl, carboxy-lower alkyl, formidoyl, acetimidoyl and benzimidoyl, R 8  and R 9  are the same or different and are selected from the group consisting of hydrogen, lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, methoxy-lower alkyl, amino-lower alkyl, lower alkoxycarbonyl, carboxy-lower alkyl, C 3  -C 5  -cycloalkyl, benzyl, acetyl, benzoyl, trifluoroacetyl, lower alkoxycarbonyl and benzyloxycarbonyl and l stands for an integer of 1 to 3, m is 1, n' is an integer of 1-4, o is an integer of 0 or 1, p an integer of 0-2, and q an integer of 0 or 1, the sum of o+p+q being 2; and n stands for an integer of 0-2, provided that R 1  is not ethyl when R 5  is hydrogen. 
     
     
       6. An antibacterial composition comprising a carrier and, as an active ingredient, an antibacterially effective amount of the quinolone derivative or a pharmaceutically acceptable salt thereof according to claim 5.